DIAN EXR Newsletter: Vol. 6, Issue 4

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Looking Back and Giving Thanks

“This is my favorite time of year,” declared Dr. Randall Bateman at an early December DIAN-TU staff meeting. “Thanksgiving and the holiday season—they give us chance to take stock, take a breath, exhale. The work we do matters … so many people are thankful for the work we do.”

While staff year-in-review meetings aren’t unique to the DIAN studies, the DIAN-TU’s annual staff retrospective highlights one-of-a-kind accomplishments. By offering the first prevention trial for Alzheimer’s disease, targeting multiple stages of disease in an adaptive platform, and offering the first tau and amyloid combination trial, the DIAN-TU leads innovation in Alzheimer’s research findings. DIAN-TU investigators maintain an extremely high (>95%) completion rate of biomarkers: in other words, our participants consistently and faithfully contribute their blood, brain images, and cerebrospinal fluid. These contributions enable our understanding of Alzheimer’s progression—and drugs’ effects on that progression—and help pinpoint which mechanisms may be most successful in delaying or halting the disease.

What does the future hold? Our studies impact not only DIAD families, but Alzheimer’s research more broadly. Identifying new surrogate biomarkers (physical evidence that indicates whether a treatment is working) in DIAN trials would help speed up researchers’ ability to measure results in all Alzheimer’s trials. New drug compounds are being identified for future DIAN trials, perhaps leading to new options for treating disease. As the Expanded Registry continues to grow, additional families can learn about observational study and clinical trial opportunities.

These advancements are run by people: submitting grants, finalizing contracts, scheduling participant visits, answering calls and emails, delivering investigational drugs, receiving brain donations, and more additional tasks than this newsletter could list. Behind this network of investigators, study coordinators, and administrative staff members are the dedicated study participants who give of their time and energy, year after year, to enable this research. And all this is enabled by the National Institutes of Health, Alzheimer’s Association, GHR Foundation, private donors, pharmaceutical partners, and other funders. To all those who enable our research, we echo the words of Dr. Eric McDade: “This has all been fantastic work. There’s plenty to celebrate and be thankful for. Thank you all so much.”

Primary Prevention Launch

The Knight Family DIAN-TU-002 Primary Prevention trial has officially launched, enrolling its first participants in the United States. In a webinar given for DIAD family members in November 2024, Dr. Eric McDade, the trial’s principal investigator, stated, “We are extremely excited to move this forward; we have a great opportunity to have a significant effect on disease modification and prevention.” Detailed information about the Primary Prevention trial design, qualifications, and requirements can now be found online, along with a detailed Frequently Asked Questions section that addresses specific trial procedures and terms.

Individuals who carry DIAD genetic mutations as well as their family members are caregivers are able to access the November Primary Prevention webinar online with a password. (Those who do not already have the password may complete a request form on the video’s webpage.) Individuals who are interested in learning more about the trial are encouraged to join the DIAN Expanded Registry or contact a study site to discuss trial participation.

We look forward to bringing you updates about this trial in future newsletter editions. The Primary Prevention is truly a global effort, and we are excited to continue our collaboration with families and our network of sites around the world in undergoing this important study.

Take a Tour: New DIAN Website

If you’ve accessed https://dian.wustl.edu recently, you have already seen that our website has undergone changes. Staff members in the DIAN-TU administrative team, DIAN Observational Study, and DIAN Expanded Registry have been working together with a consultant team since early 2024 to craft a unified site where families, caregivers, researchers, and other collaborators can find all our studies and resources.

One highlight of the new site is our searchable video library. You can view videos by category or use search terms to find specific topics. The Family Voices section compiles individual presentations from Family Conferences and news coverage of DIAD research and individuals.

It’s now easier than ever to search for publications that use DIAN Obs and DIAN-TU data on our new Publications page. You can view a feed of the most recent publications or browse suggested search terms to guide you to a particular research topic. Seeing the breadth of topics featured here creates a deeper appreciation for the impact of the data our researchers gather and our participants provide.

You can now use an interactive map to find DIAN Obs and DIAN-TU research sites on the Our Collaborators page. Our For Investigators page also provides a one-stop shop for scholars who wish to search for and/or request data from our studies.

This redesign aims to maximize accessibility across device types, for screen readers that assist people with visual impairments, and to work with browser plugins that translate pages into the viewer’s preferred language. Please note that previous, individual language web addresses will now redirect to the DIAN homepage.

Special thanks go to DIAD family members who provided feedback on the website and to our team (Jamie Bartzel, Jennifer Beatty, Angie Ziegemeier, and Ellen Ziegemeier) for their diligence in redesigning and refining this new site to accommodate the needs of family members and research partners alike. Tour the new site, and let us know your thoughts!

2024 Conference Coverage

Catch up on the latest discoveries and conversations from Alzheimer’s disease conferences in 2024 with Alzforum’s comprehensive coverage:

• AD/PD: Advances in Science & Therapy, March 2024
• Alzheimer’s Association International Conference (AAIC), July 2024
• Clinical Trials on Alzheimer’s Disease (CTAD), October 2024

Study Opportunity for Children and Young Adults in Families with Alzheimer’s Disease

The University of California, San Francisco (UCSF) Dyslexia Center is conducting a study to better understand the development of childhood cognitive abilities in families with a history of dementia. UCSF is recruiting children ages 7-17 and young adults 18-25 years old from families with a known genetic mutation for either Alzheimer’s disease or frontotemporal dementia. Participants will not learn their mutation status. The aim of the study is to learn more about the diverse brain, behavioral, and cognitive profiles throughout the lifespan, and to assess brain development trajectories.

Participation in this study involves research visits to UCSF for tests including cognitive tests, a neurological evaluation, an MRI brain scan, and other tests. Travel reimbursement for hotel, transportation, and meals is available. Monetary compensation will also be provided for participants’ time. Please see the study’s website or email FamilyNDStudy@ucsf.edu for information.

Recent DIAN Publications

• Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits
• Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease
• Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease
• Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer’s disease

DIAN observational study and trial data are increasingly published in scientific reports to advance scientific understanding of Alzheimer’s disease. Because of this, there is a marginal risk that a participant reading or hearing of these scientific reports might guess, correctly or incorrectly, information including their own or a family member’s mutation or treatment status. We take every step to minimize this risk, including ensuring that all study data lack identifying information, but de-identified data may reveal a pattern that could suggest a person’s mutation or treatment status. You can avoid these articles or presentations related to our studies to decrease this risk.

Alzheimer’s in the News

• Alzheimer’s: Scientists Analyze Body Fluid to Find New Drugs for Disease
• Alcohol Addiction Can Trigger Onset of Alzheimer’s, Study Reveals
• New drug targets for Alzheimer’s identified from cerebrospinal fluid
• Belly fat linked to signs of Alzheimer’s 20 years before symptoms begin, study says

Happy Holidays from the Dominantly Inherited Alzheimer Network!

How do we relax and celebrate the holiday season? This year, our team funded and collected toys and assembled gift packages for children in the oncology and hematology units at Barnes Jewish Children’s Hospital in St. Louis. It’s hard to picture the organization and coordination required to run a series of clinical and observational studies. However, the pile of presents and gift wrap being sorted, bundled, and sent off to bring joy to families provides a nice visualization of our team’s capabilities!

Pictured: DIAN-TU Clinical Operations, Finance, and Administrative staff, joined by the Expanded Registry, turn a conference room full of chaos into organized, beautiful packages.

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If you are interested in research opportunities,
contact the DIAN Expanded Registry at dianexr@wustl.edu.